title: Oral levosimendan in patients with severe chronic heart failure --the PERSIST study.
abstract: BACKGROUND
  Intravenous levosimendan improves symptoms in acutely decompensated heart failure.
  
  
  OBJECTIVE
  To evaluate the effects of oral levosimendan in severe chronic heart failure (CHF).
  
  
  METHODS
  307 patients with NYHA IIIB-IV CHF were randomly assigned, double-blind, to levosimendan 1 mg once or twice daily or placebo for at least 180 days. An exploratory primary end-point, the Patient Journey, a composite consisting of repeated symptom assessments, worsening heart failure and mortality during 60 days was used. Minnesota Living with Heart Failure quality of life score (MLHFQoL) and NT-proBNP were assessed repeatedly.
  
  
  RESULTS
  Patients assigned to a lower dose of levosimendan had more severe CHF at baseline. No differences in symptoms emerged and worsening heart failure events and death were similar resulting in a similar Patient Journey score with levosimendan and placebo (p=0.567). Compared to placebo, a net improvement of 3-4 points in MLHFQoL at several time-points in favour of the combined levosimendan groups was observed (p<0.001) which was accompanied by a substantial and persistent reduction in NT-proBNP (-30-40%) (p<0.001).
  
  
  CONCLUSIONS
  Levosimendan improved QoL and decreased NT-proBNP but did not improve the Patient Journey composite in patients with severe CHF. Further research with this compound is warranted to clarify safety and efficacy.
authors.affiliation: Division of Cardiology, Helsinki University Central Hospital, Helsinki, Finland. markku.nieminen@hus.fi
authors.forename: Markku S
authors.initials: MS
authors.lastname: Nieminen
authors.forename: John G F
authors.initials: JG
authors.lastname: Cleland
authors.forename: Jaan
authors.initials: J
authors.lastname: Eha
authors.forename: Yuri
authors.initials: Y
authors.lastname: Belenkov
authors.forename: Matti
authors.initials: M
authors.lastname: Kivikko
authors.forename: Pentti
authors.initials: P
authors.lastname: Põder
authors.forename: Toni
authors.initials: T
authors.lastname: Sarapohja
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002908:Chronic Disease; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D006801:Humans; D006835:Hydrazones / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood / Q000187:drug effects; D010446:Peptide Fragments / Q000097:blood / Q000187:drug effects; D011594:Psychometrics; D011724:Pyridazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011788:Quality of Life; D012720:Severity of Illness Index; D000077464:Simendan; D011795:Surveys and Questionnaires
chemical_list: D015415:Biomarkers; D002316:Cardiotonic Agents; D006835:Hydrazones; D010446:Peptide Fragments; D011724:Pyridazines; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D000077464:Simendan